Class II histone deacetylase (Class II HDAC) (Class II HDAC)

Class II histone deacetylases (HDACs) are a distinct group of enzymes that regulate gene expression and protein function by removing acetyl groups from lysine residues on histones and various non-histone substrates [PMID: 25633101]. This class is subdivided into Class IIa (HDAC4, 5, 7, and 9) and Class IIb (HDAC6 and 10), characterized by their tissue-specific expression and ability to shuttle between the nucleus and cytoplasm in response to cellular signals [PMID: 19182770]. Class IIa HDACs are particularly known for their roles in muscle differentiation, bone development, and cardiac hypertrophy, while Class IIb members like HDAC6 are major regulators of the cytoskeleton and protein degradation pathways [PMID: 12482968]. Dysregulation of these enzymes is implicated in a wide range of diseases, including various cancers, neurodegenerative disorders, and inflammatory conditions [PMID: 28211444]. Therapeutic targeting of Class II HDACs involves small molecule inhibitors that bind to the zinc-dependent catalytic site, with several pan-HDAC inhibitors already approved for clinical use in oncology [DrugBank: DB00672]. Current drug development efforts are increasingly focused on isoform-selective inhibitors to improve efficacy and reduce the systemic toxicities associated with broad-spectrum HDAC inhibition [PMID: 23911242]. These selective agents aim to target specific pathways, such as HDAC6 inhibition for neurological or immunological conditions, without the broad epigenetic effects of Class I inhibition [PMID: 12482968].

Other names

Class IIa HDACClass IIb HDACHDAC4HDAC5HDAC6HDAC7HDAC9HDAC10Histone deacetylase 4Histone deacetylase 5Histone deacetylase 6Histone deacetylase 7Histone deacetylase 9Histone deacetylase 10Class 2 HDACHDAC II

Inhibition of the zinc-dependent catalytic domain to prevent the removal of acetyl groups from lysine residues on histones and non-histone proteins, leading to altered gene transcription and cellular signaling [PMID: 19182770, PMID: 23911242].